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McWilliams Tyson posted an update 2 months ago
Left ventricular assist device (LVAD) has been saving many lives in patients with severe left ventricular (LV) failure. Recently, a minimally invasive transvascular LVAD such as Impella enables us to support unstable hemodynamics in severely ill patients. Although LVAD support increases total LV cardiac output (COTLV) at the expense of decreases in the native LV cardiac output (CONLV), the underlying mechanism determining COTLV remains unestablished. This study aims to clarify the mechanism and develop a framework to predict COTLV under known LVAD flow (COLVAD). We previously developed a generalized framework of circulatory equilibrium that consists of the integrated CO curve and the VR surface as common functions of right atrial pressure (PRA) and left atrial pressure (PLA). The intersection between the integrated CO curve and the VR surface defines circulatory equilibrium. Incorporating LVAD into this framework indicated that LVAD increases afterload, which in turn decreases CONLV. The total LV cardiac outpuantitatively predicted the upward-shift of the total CO curve resulting from the synergistic effect of LV systolic function and LVAD support. The proposed framework can contribute to the safe management of patients with LVAD.The application of human induced pluripotent stem cell-derived cardiomyocytes (hiPSCMs) from patients is expected in disease modeling and drug screening in vitro. Dilated cardiomyopathy (DCM) is an intractable disease characterized by the impairment of systolic function and leads to severe heart failure. A number of researchers have focused on disease modeling of DCM and reproduced its pathologic phenotypes in hiPSCMs, but a robust method to evaluate the contractile properties of cardiomyocytes in vitro has not been standardized. In addition, it is unknown whether the throughput of measurements and analyses could be increased sufficiently for compound screening. Here, we reviewed the articles in which the contractile abnormalities of DCM hiPSCMs were recapitulated and assessed the trends and problems in sample preparation and evaluation. We found that single-cell level analysis was ineffective in some cases, and a tissue engineering approach has become dominant recently because of its increased efficiency in reproducing impaired contractility. We also examined two commercially available automated measurement devices with moderate throughput for motion analysis using two-dimensional hiPSCM sheets composed of originally established DCM hiPSCMs. As a result, both of the tested devices, an impedance analyzer and a video image-based cell motion analyzer, were not effective in detecting the expected reduction of contractility in the DCM clone. These findings collectively suggest that a tissue engineering approach could expand the potential of disease modeling with hiPSCMs, and so far, appropriate methods for in vitro force measurement with sufficient throughput, but without sacrificing physiological fidelity, are awaited.Women have higher risk for developing TdP in response to ventricular repolarization prolonging drugs. Hundreds of trials are administering chloroquine and hydroxychloroquine with/without azithromycin to COVID-19 patients. Cyclopamine While an overall prolonged QTc has been reported in COVID-19 patients undergoing these treatments, the question on even higher QTc elevation risk in thousands of female COVID-19 patients undergoing these treatments remains unanswered. We therefore explore data reported and shared with us to evaluate safety and efficacy of antimalaria pharmacotherapies in female COVID-19 patients. Although we observed longer mean QTc intervals in female patients in 2 of the 3 cohorts reviewed, the sex disproportionality in COVID-19 hospitalizations precludes a clear sex mediated QTc interval elevation risk association in the female COVID-19 patients undergoing acute treatment regimens. Adoption of study designs that include observation of sex mediated differential triggering of cardiac electrical activity by these drugs is warranted.Background Coronavirus disease 2019 (COVID-19) is rapidly spreading and resulting in a significant loss of life around the world. However, specific information characterizing cardiovascular changes in COVID-19 is limited. Methods In this single-centered, observational study, we enrolled 38 adult patients with COVID-19 from February 10 to March 13, 2020. Clinical records, laboratory findings, echocardiography, and electrocardiogram reports were collected and analyzed. Results Of the 38 patients enrolled, the median age was 68 years with a slight female majority (21, 55.3%). Nineteen (50.0%) patients had hypertension. Seven (33.3%) had ST-T segment and T wave changes, and four (19%) had sinus tachycardia. Twenty (52.6%) had an increase in ascending aorta (AAO) diameter, 22 (57.9%) had an increase in left atrium (LA) size, and 28 (73.7%) presented with ventricular diastolic dysfunction. Correlation analysis showed that the AAO diameter was significantly associated with C-reactive protein (r = 0.4313) and creatine kinase-MB (r = 0.0414). LA enlargement was significantly associated with C-reactive protein (r = 0.4377), brain natriuretic peptide (r = 0.7612), creatine kinase-MB (r = 0.4940), and aspartate aminotransferase (r = 0.2947). Lymphocyte count was negatively associated with the AAO diameter (r = -0.5329) and LA enlargement (r = -0.3894). Conclusions Hypertension was a common comorbidity among hospitalized patients with COVID-19, and cardiac injury was the most common complication. Changes in cardiac structure and function manifested mainly in the left heart and AAO in these patients. Abnormal AAO and LA size were found to be associated with severe inflammation and cardiac injury. Alternatively, ascending aortic dilation and LA enlargement might be present before infection but characterized the patient at risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.The sterol 14α demethylase enzyme (CYP51) is an important target of fungal infections. However, the molecular mechanism between triazoles inhibitors and CYP51 remains obscure. In this study, we have investigated the binding mechanism and tunnel characteristic upon four triazoles inhibitors with CYP51 based on the molecular docking and molecular dynamics simulations. The results indicate the four inhibitors stabilize in the binding cavity of CYP51 in a similar binding mode. We discover a hydrophobic cavity (F58, Y64, Y118, L121, Y132, L376, S378, S506, S507, and M508) and the hydrophobic interaction is the main driving force for inhibitors binding to CYP51. The long-tailed inhibitors (posaconazole and itraconazole) have stronger binding affinities than short-tailed inhibitors (fluconazole and voriconazole) because long-tailed inhibitors can form more hydrophobic interactions with CYP51. The tunnel 2f is the predominant pathway for inhibitors ingress/egress protein, which is similar to the other works of CYP51.
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